Li Xuejuan, Zhang Xiaoyan, Li Xiaoyan, Ding Fangrui, Ding Jie
Department of Pediatrics, Peking University First Hospital, No.1 Xi An Men Da Jie, Beijing 100034, China.
Int J Mol Sci. 2014 Apr 17;15(4):6657-73. doi: 10.3390/ijms15046657.
Survivin is a member of the inhibitor of apoptosis protein family, which uniquely promotes mitosis and regulates apoptosis in cancer cells. Recent studies have demonstrated that survivin also expresses in several normal adult cells. In the present study, we aimed to investigate the function of survivin in the terminally differentiated epithelial cells, podocytes.
Survivin expression and location were detected by Quantitative Real-Time PCR, western blot and fluorescence confocal microscopy methods in normal and injured mouse podocytes. Cyto-protection function of survivin was also studied in cultured podocyte injured by puromycin aminonucleoside (PAN), transfected with survivin siRNA to down-regulate survivin expression, or with survivin plasmid to transiently over-express survivin.
In podocytes, PAN stimulated expressions of survivin and the apoptosis related molecule caspase 3. Knockdown of survivin expression by siRNA increased the activation of caspase 3, induced podocyte apoptosis and remarkable rearrangement of actin cytoskeleton. Moreover, over-expression of survivin inhibited PAN-induced podocyte apoptosis and cytoskeleton rearrangement.
Our data provides the evidence that survivin plays an important role in protecting podocytes from apoptosis induced by PAN. The mechanism of survivin related anti-apoptosis may, at least partially, be through the activation of caspase 3.
Survivin是凋亡抑制蛋白家族的成员，它独特地促进有丝分裂并调节癌细胞的凋亡。最近的研究表明，Survivin也在几种正常成年细胞中表达。在本研究中，我们旨在探讨Survivin在终末分化上皮细胞——足细胞中的功能。
采用定量实时PCR、蛋白质免疫印迹和荧光共聚焦显微镜方法检测正常和损伤小鼠足细胞中Survivin的表达及定位。还在经嘌呤霉素氨基核苷（PAN）损伤的培养足细胞中研究Survivin的细胞保护功能，这些足细胞转染了Survivin siRNA以下调Survivin表达，或转染了Survivin质粒以瞬时过表达Survivin。
在足细胞中，PAN刺激了Survivin和凋亡相关分子caspase 3的表达。通过siRNA敲低Survivin表达增加了caspase 3的激活，诱导了足细胞凋亡和肌动蛋白细胞骨架的显著重排。此外，Survivin的过表达抑制了PAN诱导的足细胞凋亡和细胞骨架重排。
我们的数据提供了证据，表明Survivin在保护足细胞免受PAN诱导的凋亡中起重要作用。Survivin相关抗凋亡的机制可能至少部分是通过激活caspase 3。
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